Secondary analyses of large databases derived from clinical trials of various antiviral agents have suggested recently that there may be racial disparities in response to therapy for hepatitis C. Sustained response rates in African American patients appear to be significantly less than in Caucasian patients treated with the same regimens. This proposal will focus on the design of a collaborative multicenter trial that will establish response rates is African Americans to the newest generation of medications for the treatment of chronic hepatitis C and determine if racial differences in response to therapy persist for these newer agents. Our proposal to participate as a Clinical Center for this cooperative study will emphasize the experience, unique attributes, and patient population of the Liver Program at the University of North Carolina at Chapel Hill that will ensure successful completion of this collaborative project. In this clinical trial, well-defined cohorts of African American and Caucasian patients with chronic hepatitis C (all genotype 1) will be treated with combination therapy (pegylated interferon and ribavirin) to determine differences in virological response rates between the two races. The data generated from this trial will be used to investigate baseline clinical, biochemical and virological factors associated with resistance to therapy among African Americans and a matched cohort of Caucasians. We will establish which factors are most predictive of sustained response and how they may differ between racial groups. In addition, we will determine if HCV viral kinetics differ between the cohort of African Americans and Caucasians. In patients who do not respond to therapy, we will evaluate histologic responses by comparing histologic activity in pretreatment and posttreatment liver biopsies. This information may lead to alternative strategies for managing virologic non-responders in the African American population. We will use novel methods to measure adherence to the protocol and evaluate if there are racial differences in adherence and functional health literacy. This study will also serve as a source of clinical data and clinical specimens to be used for basic science investigations into potential mechanisms of antiviral resistance in African Americans with chronic hepatitis C.